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Objective Acoustic therapies including hearing aids and tinnitus control instruments are widely used in Japan but without high levels of evidence. The outpatient hearing aid clinic at our institution fits patients with hearing aids and instructs patients on how to use them to control tinnitus if present. In this study, we examined the effects of this approach on tinnitus. Methods One hundred and eleven of 138 patients who visited our hearing aid clinic from April 2016 to September 2018 purchased hearing aids after fitting. Sixty-six of these patients (31 men, 35 women; mean age 78.0 ± 8.0 years) had both hearing loss and tinnitus and were enrolled. The tinnitus was bilateral in 41 patients and unilateral in 25 (poor hearing ear, n = 16, good hearing ear, n = 9). Hearing aids were worn bilaterally by 23 patients and unilaterally by 43 (89 devices). Seventeen of the 23 patients wearing bilateral hearing aids had bilateral tinnitus and 6 had unilateral tinnitus, i.e., in 40 ears, the tinnitus side matched the hearing aid side (40 devices) and in 6 ears did not (6 devices). Twenty-four of 43 patients wearing unilateral hearing aids had bilateral tinnitus, meaning that in 24 ears the tinnitus side matched the hearing aid side (24 devices). In six of the remaining 19 cases with unilateral tinnitus, the hearing aid and tinnitus were on the same side (6 devices) and in 13 were on opposite sides (13 devices). Changes in the Tinnitus Handicap Inventory (THI), visual analog scale (VAS, for tinnitus discomfort, severity, and persistence), and Hospital Anxiety and Depression Scale scores were measured immediately before using a hearing aid and 12 months later. Results Significant effects of hearing aids on tinnitus were observed in all subjects (THI, p = 0.0000030), VAS (severity, p = 0.000000066; discomfort, p = 0.0000013). Significant effects were observed with bilateral hearing aids (THI, p = 0.0012; VAS for severity, p = 0.00069; VAS for discomfort, p = 0.00052) and with unilateral hearing aids (THI, p = 0.00055; VAS for severity, p = 0.000034; VAS for discomfort, p = 0.00007). Spearman's rank correlation coefficient showed a significant positive correlation between the THI and VAS scores (p = 0.0033). In cases of bilateral tinnitus, significant differences were observed with bilateral hearing aids (THI, p = 0.011; VAS for severity, p = 0.0019; VAS for discomfort; p = 0.020) and with unilateral hearing aids (THI, p = 0.00069; VAS for severity, p = 0.00071; VAS for discomfort, p = 0.000093). Conclusion Acoustic therapy using hearing aids was effective for tinnitus. Even when bilateral, a unilateral hearing aid is able to improve tinnitus. When unilateral, the ipsilateral hearing aid is able to improve tinnitus.

Synthetic excitatory synaptic organizer The human brain contains trillions of synapses within a vast network of neurons. Synapse remodeling is essential to ensure the efficient reception and integration of external stimuli and to store and retrieve information. Building and remodeling of synapses occurs throughout life under the control of synaptic organizer proteins. Errors in this process can lead to neuropsychiatric or neurological disorders. Suzuki et al. combined structural elements of natural synaptic organizers to develop an artificial version called CPTX, which has different binding properties (see the Perspective by Salinas). CPTX could act as a molecular bridge to reconnect neurons and restore excitatory synaptic function in animal models of cerebellar ataxia, familial Alzheimer's disease, and spinal cord injury. The findings illustrate how structure-guided approaches can help to repair neuronal circuits. Science , this issue p. eabb4853 ; see also p. 1052

A mouse model of epilepsy was generated by inducing status epilepticus (SE) for either 1.5 or 4.5h with pilocarpine to study anxiety-related behaviors, changes in the electroencephalogram of the cerebral cortex and hippocampus, and expression of hippocampal proteins. The viability and rate of success of SE induction were high in C57BL/6N mice but not in C57BL/6J mice. C57BL/6N mice were immotile during the first 2days after SE; however, by the third day, most mice were recovered and exhibited strong anxiety-related behaviors in response to the light/dark preference test and open field test. There was a striking difference in the temporal appearance of anxiety-related behavior between the two SE durations: 1.5h SE mice exhibited strong anxiety-related behavior 3days after SE that gradually attenuated over the next few weeks, whereas 4.5h SE mice exhibited strong anxiety-related behavior 3days after SE that persisted even at nearly 1year after SE. Mice receiving both SE durations exhibited generalized seizures (GS) after SE; however, there was a marked difference in the timing and duration of GS appearance. Mice in the 4.5h SE group exhibited spontaneous GS from 4days to at least 96days after SE. In contrast, mice in the 1.5h SE group exhibited GS only within the first several days after SE; however, epileptic spike clusters continuously appeared in the cerebral cortex and hippocampus for up to twelve days after SE. Among the hippocampal proteins tested, only brain derived-neurotrophic factor (BDNF) exhibited altered expression in parallel with anxiety-related behavior. These results showed the possibility that BDNF expression in the hippocampus might cause anxiety-related behavior in adulthood.

A linearly polarized hard X-ray photoemission system has been developed for studying the ground-state symmetry of strongly correlated materials., An angle-resolved linearly polarized hard X-ray photoemission spectroscopy (HAXPES) system has been developed to study the ground-state symmetry of strongly correlated materials. The linear polarization of the incoming X-ray beam is switched by a transmission-type phase retarder composed of two diamond (100) crystals. The best value of the degree of linear polarization was found to be −0.96, containing a vertical polarization component of 98%. A newly developed low-temperature two-axis manipulator enables easy polar and azimuthal rotations to select the detection direction of photoelectrons. The lowest temperature achieved was 9 K, offering the chance to access the ground state even for strongly correlated electron systems in cubic symmetry. A co-axial sample monitoring system with long-working-distance microscope enables the same region on the sample surface to be measured before and after rotation. Combining this sample monitoring system with a micro-focused X-ray beam by means of an ellipsoidal Kirkpatrick–Baez mirror (25 µm × 25 µm FWHM), polarized valence-band HAXPES has been performed on NiO for voltage application as resistive random access memory to demonstrate the micro-positioning technique and polarization switching.

The cerebellum is thought to be involved in cognitive functions in addition to its well established role in motor coordination and motor learning in humans. Cerebellin 1 (Cbln1) is predominantly expressed in cerebellar granule cells and plays a crucial role in the formation and function of parallel fiber–Purkinje cell synapses. Although genes encoding Cbln1 and its postsynaptic receptor, the delta2 glutamate receptor (GluD2), are suggested to be associated with autistic-like traits and many psychiatric disorders, whether such cognitive impairments are caused by cerebellar dysfunction remains unclear. In the present study, we investigated whether and how Cbln1 signaling is involved in non-motor functions in adult mice. We show that acquisition and retention/retrieval of cued and contextual fear memory were impaired inCbln1-null mice.In situhybridization and immunohistochemical analyses revealed that Cbln1 is expressed in various extracerebellar regions, including the retrosplenial granular cortex and the hippocampus. In the hippocampus, Cbln1 immunoreactivity was present at the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare without overt mRNA expression, suggesting that Cbln1 is provided by perforant path fibers. Retention/retrieval, but not acquisition, of cued and contextual fear memory was impaired in forebrain-predominantCbln1-null mice. Spatial learning in the radial arm water maze was also abrogated. In contrast, acquisition of fear memory was affected in cerebellum-predominantCbln1-null mice. These results indicate that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially and that Cbln1 signaling likely regulates motor and non-motor functions in multiple brain regions.SIGNIFICANCE STATEMENTDespites its well known role in motor coordination and motor learning, whether and how the cerebellum is involved in cognitive functions remains less clear. Cerebellin 1 (Cbln1) is highly expressed in the cerebellum and serves as an essential synaptic organizer. Although genes encoding Cbln1 and its receptor are associated with many psychiatric disorders, it remains unknown whether such cognitive impairments are caused by cerebellar dysfunction. Here, we show that Cbln1 is also expressed in the forebrain, including the hippocampus and retrosplenial granular cortex. Using forebrain- and cerebellum-predominant conditionalCbln1-null mice, we show that Cbln1 in the forebrain and cerebellum mediates specific aspects of fear conditioning and spatial memory differentially, indicating that Cbln1 signaling regulates both motor and non-motor functions in multiple brain regions.

An attempt to reduce the SET voltage and RESET current of resistive switching (RS) memory was made using a geometric array of nanopeak (NP) structures. Bottoms of anodic porous alumina were used to form the NP structures that act as guides for the formation of conductive filaments that effectively concentrate the electric field. Samples were fabricated with flat surfaces (FS) and with two types of NP structure with different NP pitch. The NP samples provided SET voltages less than 2 V with narrow distributions and the RESET current was lower than that with the FS sample.

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From the point of view to design a practical shock-in-rotor type rotor, the quasi-axisymmetric flow in the subsonic region is considered in the case having the uniform flow with no swirl components at the inlet of rotor blades.The flow in the supersonic region is assurned to be parallel to the axis and satisfy radial equilibrium before the normal shock. The turning angle from the inlet to the normal shock is given.In this report the flow calculation is carried out by giving two conditions (1) angular spacing and (2) angular momentum in the eubsonic region and is applicable to the example with known shapes of both inner and outer casings. The results show the possibilities to design a blade passage for practical use.

A possibility of two-dimensional supersonic portion having quasi-axisymmetric flows which satisfy simplified radial equilibrium is investigated in this report. With the intension of getting a supersonic portion for practical use, the main requirements are given as follows. (1) The inlet flow is uniform and parallel to the axis. (2) The flow just before the normal shock is quasi-axisymmetric and satisfies simplified radial equilibrium. (3) The starting condition for a supersonic diffuser is satisfied between the inlet flow and the flow just before the normal shock. (4) The turning angle and the magnitude of deceleration in the supersonic portion are specified for the purpose of adequate blade thickness. The calculated examples are obtained at hub, mean and tip radii.

A method of designing latticed wing profile with prescribed velocity distribution along wing surface (not chordwise direction) is explained. Latticed wing with small pitch-chord ratio, large camber and large thickness can be treated with fair eassiness. The full paper in English will be published in "The Report of Transportation Technical Research Institute" in near future.

A method of solution for latticed wing of arbitrary profile is presented. The profile-surface is regarded as single vortex sheet, and potential theory is applied. Thus we get an integral equation concerning to the velocity potential. By successive approximation we can get the solution. High solidity, camber, thickness do not prevent the solution, and moreover it requires less labour than the methods ever presented.But the facts that we must prescribe the discharge direction, and that we must repeat the same process to get the solution with different inlet direction, are the faults of this method.

In measuring high subsonic internal flows which are observed in high speed turbomachines such as transonic or supersonic compressors, authors planned to use a cylindrical probe which was supported at both ends, and got satisfactory results in the case of zero inclination angle.Furthermore, the inclination characteristics of this probe were investigated experimentally and it was revealed that the yaw angle of flow could be easily obtained independently of both Mach number M∞ and inclination angle α. It was also revealed that the flow component normal to the axis of the probe (total pressure P0, Mach number M∞) could be obtained with a fair accuracy from the characteristics of zero inclination angle within the range of not too large inclination angles (about ±15 degrees).

The writer has calculated Air speed distribution of flat plate infinite multiplane by means of conformal transformation method. It is thought that the obtained values themselves are not important, but the qualitative tendency of derived curves is useful for the study of infinite multiplane. This report is one of"Study of Axial Flow Machine Series". They were published on the"Journal of the Aeronautical Institute of Tokyo Imperial University"and the"Report of the Institute of Science and Technology of University of Tokyo".

Performances of the compressor type cascade of blades with small aspect ratio AR were experimentally obtained at the center of blade span. All blades had same span of 50mm and their aspect ratio were 2.08, 1.39, 1.04 and 0.83. Stagger angle (α) was changed from 0° to 60° and attack angle (αi) from 0° to 15°. Results indicate that total pressure loss coefficient takes a minimum value at AR_??_1 irresspectively of α and αi. At αi over about 5° turning angle (e) increases and at αi=0° it decreases gradually with increasing AR. Axial velocity ratio, in the case α=0°, decreases gradually with incresing AR, and in the case α=30° it keeps almost constant value irrespectively of AR at αi=constant, but in cases α=50° and 60° it increases at αi≥5-10° with increasing AR.

Snap25(S187A/S187A) mouse is a knock-in mouse with a single amino acid substitution at a protein kinase C-dependent phosphorylation site of the synaptosomal-associated protein of 25 kDa (SNAP-25), which is a target-soluble NSF attachment protein receptor (t-SNARE) protein essential for neurotransmitter release. Snap25(S187A/S187A) mice exhibit several distinct phenotypes, including reductions in dopamine and serotonin release in the brain, anxiety-like behavior, and cognitive dysfunctions. Homozygous mice show spontaneous epileptic convulsions, and about 15% of the mice die around three weeks after birth. The remaining mice survive for almost two years and exhibit spontaneous recurrent seizures throughout their lifetime. Here, we conducted long-term continuous video electroencephalogram recording of the mice and analyzed the process of epileptogenesis and epileptic maturation in detail. Spikes and slow-wave discharges (SWDs) were observed in the cerebral cortex and thalamus before epileptic convulsions began. SWDs showed several properties similar to those observed in absence seizures including (1) lack of in the hippocampus, (2) movement arrest during SWDs, and (3) inhibition by ethosuximide. Multiple generalized seizures occurred in all homozygous mice around three weeks after birth. However, seizure generation stopped within several days, and a seizure-free latent period began. Following a spike-free quiet period, the number of spikes increased gradually, and epileptic seizures reappeared. Subsequently, spontaneous seizures occurred cyclically throughout the life of the mice, and several progressive changes in seizure frequency, seizure duration, seizure cycle interval, seizure waveform, and the number and waveform of epileptic discharges during slow-wave sleep occurred with different time courses over 10 weeks. Anxiety-related behaviors appeared suddenly within three days after epileptic seizures began and were delayed markedly by oral administration of valproic acid. These results showed that Snap25(S187A/S187A) mice exhibited a variety of epilepsy-related phenomena, and thus, they will be useful for understanding the mechanisms of epileptogenesis, epileptic maturation, and the actions of antiepileptic drugs.

Squire and Winter solved secondary flow problem by replacing the boundary layer with vorticity. They used curvilinear coordinates and is pretty complex. Hawthorne presented another method founded on the same idea using vector analysis after that, but his method is also inaccessible.The writer presents in this paper an easy method based on the rule of vortex motion, and has obtained the same results of 1st approximation as that of Squire, Winter and Hawthorne.

Background Synaptosomal-associated protein, 25 kDa (SNAP-25) regulates the exocytosis of neurotransmitters. Growing evidence suggests that SNAP-25 is involved in neuropsychiatric disorders, such as schizophrenia, attention-deficit/hyperactivity disorder, and epilepsy. Recently, increases in anxiety-related behaviors and epilepsy have been observed in SNAP-25 knock-in (KI) mice, which have a single amino acid substitution of Ala for Ser187. However, the molecular and cellular mechanisms underlying the abnormalities in this mutant remain unknown. Results In this study, we found that a significant number of dentate gyrus (DG) granule cells was histologically and electrophysiologically similar to immature DG neurons in the dentate gyrus of the adult mutants, a phenomenon termed the “immature DG” (iDG). SNAP-25 KI mice and other mice possessing the iDG phenotype, i.e., alpha-calcium/calmodulin-dependent protein kinase II heterozygous mice, Schnurri-2 knockout mice, and mice treated with the antidepressant fluoxetine, showed similar molecular expression patterns, with over 100 genes similarly altered. A working memory deficit was also identified in mutant mice during a spontaneous forced alternation task using a modified T-maze, a behavioral task known to be dependent on hippocampal function. Chronic treatments with the antiepileptic drug valproate abolished the iDG phenotype and the working memory deficit in mutants. Conclusions These findings suggest that the substitution of Ala for Ser187 in SNAP-25 induces the iDG phenotype, which can also be caused by epilepsy, and led to a severe working memory deficit. In addition, the iDG phenotype in adulthood is likely an endophenotype for at least a part of some common psychiatric disorders.